Paper strip with color-indicated proteins (Wyss Institute, Harvard University)
24 October 2014. Biomedical engineers at Harvard University designed systems with simple sensors applied on paper to detect complex cellular reactions that can speed use of point-of-care diagnostics in the field. Findings from the team at Harvard’s Wyss Institute for Biologically Inspired Engineering, with colleagues from Boston University and Howard Hughes Medical Institute in Chevy Chase, Maryland, appear in two articles published yesterday in the journal Cell (paid subscription required).
Both papers, from the labs of Wyss Institute faculty Peng Yin and James Collins, seek to make it possible for advances in synthetic biology to reach researchers and clinicians outside the controlled environments of laboratories. “Synthetic biology,” says Collins in a university statement, “has been confined to the laboratory, operating within living cells or in liquid–solution test tubes.”
Using paper as a test environment, say the researchers, takes more than transferring lab processes to a new medium, but the development of what Collins calls a “sterile, abiotic operating system upon which we can rationally design synthetic, biological mechanisms to carry out specific functions.” Keith Pardee, staff scientist and first author of the first Cell paper, devised a process with proteins that illuminate and change colors to provide detection of biochemical changes.
“We’ve harnessed the genetic machinery of cells and embedded them in the fiber matrix of paper, which can then be freeze dried for storage and transport,” notes Pardee. Freeze-drying makes it possible to store the paper strips at room temperature for up to a year. Technicians in the field then only need to add water to activate the paper strips.
The researchers devised several types of paper strips in the study containing detectors for small-molecule and RNA mechanisms. Among the proof-of-concept tests devised were sensors for glucose and antibiotic–resistant bacteria, as well as a detector to determine different strains of the Ebola virus. Pardee says the paper-based system makes it possible to return results in 90 minutes or less for some tests now taking 2 to 3 days. The Ebola strain detector, for example, returns results in about an hour.
The paper-based sensors in the first study applied a development described in the second Cell study, programmable circuits designed from scratch to regulate the expression of genes. “We looked at our progress to rationally design dynamic DNA nanodevices in test tubes,” says senior author Yin, and applied that same fundamental principle to solve problems in synthetic biology.” The bio-circuits, called toehold switches, are designed to detect RNA signatures, then produce a specific protein.
Postdoctoral fellow Alex Green, first author of the second paper, applied his previous work in materials science and software engineering to devise the programmable bio-circuit technology. Lab tests of the circuits show they regulate all-synthetic gene expression some 40 times better than controllers adapted from natural elements. The reliability of the bio-circuits makes it possible to link them together into more complex devices performing multiple functions, such as detecting a bacteria or virus and releasing a specific drug in response.
The following video tells more about and demonstrates the technologies described in the two studies.
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